Transcatheter aortic valve replacement (TAVR) has emerged as a transformative intervention in the management of aortic stenosis (AS), significantly improving the symptoms and survival outcomes of elderly patients afflicted by this progressive disease [1]. A notable proportion of individuals with severe AS who undergo TAVR, estimated to range from 60% to 80%, also present with concurrent coronary artery disease (CAD) [2]. This dual pathology is largely driven by shared risk factors such as diabetes, systemic inflammation, gender, and advancing age. The interplay between AS and CAD is characterized by a heightened cardiac workload resulting from AS, which can then exacerbate myocardial ischemia associated with CAD [3, 4]. Conversely, the presence of CAD hampers the heart’s ability to compensate for the increased hemodynamic demands imposed by AS, leading to an accelerated onset of symptoms and the emergence of more severe complications [5].

The use of computed tomography (CT) has become increasingly widespread during the assessment of patients with severe AS for TAVR. CT enhances the diagnostic accuracy and facilitates more effective management strategies [6, 7]. Among the innovations in this area, the analysis of pericoronary adipose tissue (PCAT) has gained attention as a promising non-invasive biomarker for vascular inflammation [8]. PCAT serves as a novel tool for stratifying patients with cardiovascular disease [9]. Extensive research has shown that elevated PCAT attenuation, a marker of increased inflammatory activity, is strongly correlated with a higher risk of major adverse cardiac events (MACE) and worse clinical outcomes [10, 11]. This association highlights the critical involvement of inflammatory mediators, such as interleukins and tumor necrosis factor-alpha, in the processes of tissue remodeling, calcification, and plaque instability, all of which contribute to cardiovascular risk [12]. The role of PCAT in mediating these inflammatory pathways underscores its potential utility as a prognostic marker.

Based on prior literature, we hypothesized that PCAT analysis of the culprit vessel or of the post-stent implantation vessel subsequent to TAVR could be instrumental in identifying patients at high risk for MACE. Therefore, the aim of this study was to evaluate the prognostic significance of coronary PCAT measured three months post-TAVR in predicting cardiovascular events among CAD patients.

This study found that measurement of PCAT attenuation by CCTA three months after TAVR could effectively predict MACE in patients with obstructive CAD. The key finding was that high PCAT attenuation was associated with a significantly increased risk of MACE, with a cutoff threshold of –67.5 HU demonstrating high sensitivity and specificity for predicting adverse outcomes. These results highlight the potential of PCAT attenuation appears to be a promising marker for risk stratification in this high-risk patient population.

The risk factors for AS overlap significantly with those for atherosclerosis, explaining why $>$50% of patients with severe symptomatic AS also present with concurrent CAD. However, the management of CAD in the context of TAVR remains challenging due to the lack of large randomized controlled trials (RCTs) and the exclusion of patients with significant CAD in previous studies on TAVR [17]. Steyer et al. [18] previously reported that PCAT attenuation in the RCA, measured pre-TAVR, was a significant predictor of outcomes in AS patients undergoing TAVR [19]. Our study differs in that we assessed PCAT attenuation post-TAVR and evaluated the most diseased coronary segment, rather than focusing exclusively on the RCA. Contrary to previous reports, we did not find that PCAT attenuation in any specific coronary artery was singularly predictive of MACE. This observation aligns with the findings of Meng et al. [20] and Napoli et al. [21] who reported that higher PCAT attenuation was associated with adverse outcomes in CAD patients, including myocardial infarction and cardiovascular mortality. However, our study advances the field by specifically addressing TAVR patients, a subgroup with both AS and CAD. These patients present a unique challenge in risk stratification. Our results suggest that PCAT attenuation could prove valuable in determining the prognosis of post-TAVR patients, thereby improving risk prediction. Furthermore, when integrated into multivariable models, PCAT attenuation enhanced the prognostic value of traditional clinical and imaging markers, such as valve calcification and NYHA functional class, thus offering incremental predictive value over established markers. This underscores the potential of PCAT attenuation as a non-invasive and robust biomarker in the post-TAVR setting, which may contribute to better patient management and outcomes.

PCAT has emerged as a promising biomarker for assessing coronary inflammation and plaque stability [22]. With the increasing incidence of AS and subsequent rise in TAVR procedures, the need for reliable markers to predict postoperative outcomes in CAD patients is becoming more critical. The utility of PCAT in this context has been substantiated by numerous studies, including the Comprehensive Risk Prediction in Surgery (CRISP-CT) study, which underscores the ability of PCAT attenuation to predict mortality risk [23]. Furthermore, Elnabawi et al. [24] highlighted the versatility of PCAT by demonstrating its effectiveness in tracking therapeutic responses in CAD, thus expanding its application beyond mere prognostication [25].

The role of PCAT has assumed greater significance in the post-TAVR landscape, with the procedure itself capable of inducing biological and physical stresses on the coronary vessels. This is particularly evident in the hemodynamic changes brought about by the newly implanted aortic valve, which directly influence myocardial oxygen supply and demand [26]. In the case of a prosthesis-patient mismatch or suboptimal deployment of the valve, the anticipated alleviation of myocardial ischemia may not be fully realized. Such instances can lead to inadequate coronary perfusion, especially in patients with existing CAD [27]. Moreover, the postoperative phase can invoke systemic inflammatory responses, potentially accelerating the progression of atherosclerosis and contributing to plaque vulnerability [28, 29]. Collectively, these factors have significant implications for the long-term cardiac prognosis of CAD patients post-TAVR.

Currently, there is significant debate regarding prognostic markers for CAD combined with AS after TAVR. Examples of such markers include the Duke Myocardial Jeopardy Score (DMJS) and the QCA-derived SYNTAX Score (SS), both of which are based on invasive angiography [30, 31]. However, these scoring systems were developed based on CAD patients without consideration of the overall impact on the heart when AS is also present. Spatial changes in PCAT attenuation in CCTA images can reflect changes in the entire heart after TAVR. Our study found that PCAT attenuation levels were notably higher in patients who suffered a MACE. The elevated attenuation reflects a heightened inflammatory state within the coronary vasculature, which is detectable and quantifiable through CCTA. After adding PCAT as a predictor, the C-index and IDI of conventional clinical models increased by 0.82 and 55%, respectively. Interestingly, we also found that revascularization in CAD patients does not influence PCAT attenuation. This relationship persisted irrespective of whether patients had undergone revascularization procedures, underscoring the robustness of PCAT as an independent prognostic tool.

Our study has several limitations. Firstly, as this retrospective study derived the PCAT threshold from a single-center cohort and the same study population, the results lack external validation and may overestimate real-world performance. Thus, future multicenter studies with large sample sizes are needed to confirm the generalizability of these findings. Since this study focused on CAD patients post-TAVR, the applicability of our findings to other populations, such as patients with acute coronary syndrome or prior revascularization, remains to be determined. The median follow-up of 1.5 years may not be sufficient to fully capture long-term events, and insufficient time may have elapsed for patients with shorter follow-up to experience late complications. Furthermore, PCAT attenuation was measured three months post-TAVR, thus excluding patients with early events and introducing potential immortal time bias that could overestimate the prognostic value of PCAT. Studies with longer follow-up times are needed to confirm the sustained predictive ability of PCAT post-TAVR.

In conclusion, the ability of PCAT to serve as a non-invasive, quantifiable marker of coronary inflammation makes it a promising candidate for predicting the outcome of obstructive CAD following TAVR. The sensitivity of PCAT to changes in the inflammatory state and its correlation with clinical outcomes highlight its superiority and potential as a standard component of post-TAVR patient assessment.

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

TTH and JZS contributed to the study design, statistical analysis and reviewing it critically for important intellectual content. SXL and XHW wrote the original draft and contributed to image analysis and reviewed the manuscript for important intellectual content. XFD provided scientific direction and made substantial contributions to the study conception and design, as well as to writing and revising the manuscript. JZS coordinated the collection of clinical data and CT scans and use and commissioning of frontier for Syngovia. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Human Research Ethics Committee of the Second Affiliated Hospital, Zhejiang University School of Medicine (Approval No: I2024025). Given the retrospective nature of the study, the Ethics Committee waived the requirement for written informed consent. All patient data were anonymized and handled confidentially in compliance with institutional and national ethical standards.

The authors thank each of the study subjects for their participation.

This study has received funding by The Medical Science and Technology Project of Zhejiang Province, China (Grant Numbers 2021KY393) and The National Key Research and Development Program of China (grant No. 2018YFE0198400).

The authors declare no conflict of interest.